A variety of previous studies indicate that symptomatic, and, in some cases, remitted depressed patients differ from normals in one or more of the following: REM latency, DST status, subjective and neuroendocrine response to cholinergic agonists, RBC choline, and fibroblast muscarinic receptor counts. These data support the notion that CNS cholinergic systems are hypersensitive in some depressions. Two experiments are planned to test this hypothesized cholinergic CNS abnormality. Different individuals will be used in each experiment. Five subject groups will be studied: (1) symptomatic, unipolar, endogenous, major depressions (ED) with short REM latencies (n=20); (2) symptomatic, unipolar, nonendogenous (NED) major depressions with normal REM latencies (n=20); (3) remitted (ED) depressions (n = 12); (4) remitted (NED) depressions (n = 12); and (5) normal controls without a personal or family history of depression (n=20). Experiment 1 will determine whether these groups differ in the latency to REM induced by 0.5 mg i.v. arecoline and will establish the test-retest reliability of this challenge test. Experiment 2 will determine whether these subject groups differ in their behavioral, neuroendocrine, or regional cerebral blood flow responses to 1.0 mg i.v. arecoline and will develop test-retest information on this challenge test. Results should identify which depressions evidence CNS cholinergic hypersensitivity; (2) determine which test method is more specific, sensitive, and reliable; (3) determine whether remitted depressed continue to display this abnormality, and (4) identify the cortical/subcortical structures that contribute to the abnormality.